DESCRIPTION Background/Rationale: Someone has a stroke in the US every 45 seconds resulting in over 700,000 new strokes every year and stroke is the leading cause of disability in our veterans. The vast majority of these cases results in motor impairments, particularly in upper extremity function. The predominant treatment of impaired upper extremity function is motor learning based rehabilitation. However, empirical research of motor learning has had little impact on stroke rehabilitation. Specifically, the motor learning research suggests that limiting the amount of explicit knowledge during motor learning may improve retention and reduce cognitive workload. Operant conditioning based learning strategies reduce explicit knowledge compared to error-based learning strategies (the latter are commonly used in clinical rehabilitation). Thus the aim of the current study is to determine the effect of different learning strategies during motor learning on functional outcomes (i.e. motor performance, retention, and cognitive workload). In addition, to determine if explicit knowledge mediates the impact of learning strategy on these variables, a second study will be conducted. In this study the neural substrate underlying explicit knowledge (left temporal region) will be inhibited using repetitive transcrania magnetic stimulation (rTMS) while individuals are learning the same task and functional outcomes assessed. Objectives: Our preliminary data indicate that we can manipulate the amount of explicit knowledge that is formed during motor learning by changing the learning strategy. Preliminary data have suggested that the KineReach apparatus is well suited for the learning task and is able to record relevant motor performance and retention information. Finally, we have developed an objective physiological marker of cognitive workload using electroencephalography (EEG) and demonstrated the feasibility of implementing this metric in stroke patients. Importantly, this project will be completed under the advisory of four senior research personnel and the mentorship and training they will provide will guide this project as well as foster future independent research of the applicant. In addition to the proposed research project, there is a complimentary training agenda, which includes visits to both impatient and outpatient settings to observe clinical assessment/treatment. Methods: Thirty right-handed, ride-side affected subcortical chronic stroke patients will be randomly assigned to one of three groups, error-based without rTMS, error-based with rTMS or operant conditioning learning. Sample size was based on two other independent noninvasive motor learning studies which were adequately powered with a comparable N. All groups will learn a novel motor task while measures of performance and cerebral-cortical activity are recorded. The task will include center out reaching movements with the less affected arm. In study one, the groups will differ as one will receive error-based learning (with no rTMS), while the other will receive operant conditioning. In the second study the two groups that received error-bases learning will be compared, one that received rTMS and the other that did not. Finally, for both studies, all participants will return to the lab one week later and will complete a performance based retention test. Findings/Results: In study one, it is predicted that the operant conditioning group will perform the task as well as the error-based group (no rTMS), but will do so with less cognitive burden imposed, as indexed by the EEG assessment. In addition, the operant conditioning group will show greater retention of the learning as compared to the error-based group (no rTMS). In study two, it is predicted that the error-based with rTMS group will: learn as well, have reduced cognitive burden, and exhibit greater retention, as compared to the error-based (no rTMS group). Status: This project is currently in the planning and development stage. Impact: This research endeavor will guide future research projects regarding learning strategy and neurorehabilitation and potentially drive future clinical interventions for veteran stroke survivors.